The long term objective of this Program is to develop a mechanistic understanding of the causal relationship of inflammation to cancer. A specific objective is to determine the role of Nitric Oxide (NO) in the process of inflammation-induced carcinogenesis and in the maintenance of the melanoma cancer cell. The results of these investigations will be applied in a translational manner to human cancers and pre-cancerous states, including inflammatory bowel disease (IBD), colon cancer, and melanoma. The research will utilize cells in culture and animal models. The animal models will be used to develop biomarkers of inflammation chemistry that can be applied to archived human tissue to determine whether the animal model represents the human case. The biomarkers can then be used to develop a therapeutic approach to cancer prevention. This Program has already demonstrated that NO-synthase inhibitors can ameliorate the early stages of tissue changes in IBD and colon cancer in our animal models.